The short term objectives of this K02 proposal are: 1) to expand the scope the applicant's active imaging genetic R01 by adding a high-throughput genome-wide epigenetic component; 2) to actively seek additional training in the areas of statistical genetics and epigenetics; and 3) to establish new and enhance existing collaborations with prominent statistical and imaging genetics experts. The long-term objective of the K02 award is to bolster the applicant's scientific career and to further facilitate her growth into a prolific and highly successful independent investigator in the AD field. The applicant has developed an active research program focused on the imaging genetic biomarkers of AD. Her recently funded R01 award studies the associations between clinical, imaging and transcriptomic disease-associated traits in a prospective longitudinal cohort of cognitively normal and prodromal AD subjects. The objective of the science integral to this proposal is to expand the scope of the experiments to include newly acquired epigenetic data. The short-term scientific goals are to integrate epigenetics with the genomic, transcriptomic, clinical and imaging data from the parent R01 in order to elucidate the epigenetic effects on gene expression, brain atrophy, brain amyloidosis and disease risk. The long-term scientific goals of the R01 and K02 are to identify novel disease-associated pathways and therapeutic targets. To ensure the success of the proposed work, the applicant will be supported by a diverse group of distinguished collaborators with expertise in highly relevant fields and methods.